Micro-muscle in biological medium

ABSTRACT

The invention concerns a micro-muscle designed to be immersed in a biological liquid, comprising a deformable chamber whereof one portion at least consists of a semipermeable membrane, said chamber containing a solution capable of osmotic activity. The solution is preferably activated by a product to be injected into the biological liquid.

The present invention relates to devices that can be used as a temporaryor definitive actuator or endoprosthesis within a biological medium suchas the human body or an animal body.

The present invention especially finds applications as a ring-shapedendoprosthesis or stent that can be used to compensate an arterialstenosis, or as an intervention means to aid the sewing, clipping, orjointing of blood vessels, to obturate a vessel, to fill up a cavity, orto have an element such as a needle act against an internal wall of abiological medium such as a human or animal body.

Inflatable balloons or shape-memory devices, which all exhibitdisadvantages, as will be discussed hereafter, are conventionally usedto perform such operations.

More specifically, the present invention provides a micromuscle intendedto be immersed in a biological medium, comprising a deformable chamberhaving at least a portion formed of a semipermeable membrane, thischamber containing a solute likely to be osmotically active, the chamberbeing designed to have, after inflating by osmotic effect, apredetermined shape.

According to an embodiment of the present invention, the solute isactivable by a product injectable into the biological medium.

According to an embodiment of the present invention, the solute is boundto an attachment matrix from which it can detach in consequence of acompetition with another body.

According to an embodiment of the present invention, the solute is boundto HABA molecules, themselves bound to attachment matrixes by proteins,such as avidin or streptavidin derivatives, this bond being breakable bycompetition with biotin or the like.

According to an embodiment of the present invention, the solute is boundto avidin molecules, themselves bound to attachment matrixes by HABAparticles, this bond being breakable by competition with biotin or thelike.

According to an embodiment of the present invention, the molecules ofbiotin or the like are likely to be monomers or dimers.

According to an embodiment of the present invention, the solute isencapsulated in at least one envelope to be destroyed by a physical orchemical reaction.

According to an embodiment of the present invention, the solute isformed of macromolecules likely to be broken by physical or chemicalaction.

According to an embodiment of the present invention, said chambercomprises a first portion made of a resilient material of desired shape,communicating with a second portion forming a semipermeable membrane,for example in the form of fibers.

According to an embodiment of the present invention, said chamber or itsfirst resilient portion is torus-shaped.

According to an embodiment of the present invention, said chamber or itsfirst resilient portion is likely to deform longitudinally.

According to an embodiment of the present invention, said chamber or itsfirst resilient portion is a substantially spherical deformable volume.

According to an embodiment of the present invention, said chamber underits first resilient portion is formed of two half-cylinders sliding oneinside of the other.

According to an embodiment of the present invention, said chamber or itsfirst resilient portion is surrounded with sheath or net determining itsdefinitive shape.

According to an embodiment of the present invention, the solute isalbumin.

According to an embodiment of the present invention, the semipermeablemembrane of the micromuscle is in communication with a second chamberformed of a flexible material and containing a reserve of a liquidlikely to form a solution with a solute contained in the first chamber.

According to an embodiment of the present invention, the second chambercontains a solute likely to be released by physical or chemical action.

The present invention also provides a device for inserting needles intoa wall of a vessel filled with a biological liquid, comprising a guide,needles to which a wire is firmly attached on a first side of the guide,the needles being likely to be laid flat on the guide, first osmoticmicromuscles on the first side of the guide, likely to erect theneedles, and at least one second osmotic micromuscle arranged on theopposite side of the guide.

The present invention also provides a device for aiding the clippingcomprising a micromuscle insertable at the end of a cut up vessel,comprising a cylindrical body, digitized ends.

The present invention also provides a use of the above-mentionedmicromuscle, in which the micromuscle is torus-shaped and is intended tobe used as a joint at the connection between two ducts, such as acylindrical endoprosthesis and a blood vessel.

The present invention also provides a use of the above-mentionedmicromuscle, in which the micromuscle is torus-shaped, expandableoutwards and is intended to obturate a duct or a cylindricalendoprosthesis arranged in this duct.

The present invention also provides a use of the above-mentionedmicromuscle, in which the micromuscle is in the form of a bag orcylinder expandable outwards and is intended to obturate a duct.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing objects, features, and advantages of the present inventionwill be discussed in detail in the following non-limiting description ofspecific embodiments in connection with the accompanying drawings, amongwhich:

FIGS. 1A to 1C illustrate a first embodiment of a micromuscle accordingto the present invention;

FIGS. 2A to 2C illustrate a second embodiment of a micromuscle accordingto the present invention;

FIGS. 3A to 3C illustrate alternatives of a third embodiment of amicromuscle according to the present invention;

FIGS. 4A and 4B show a fourth embodiment of a micro-muscle according tothe present invention;

FIG. 5A shows a fifth embodiment of a micromuscle according to thepresent invention;

FIG. 5B shows a sixth embodiment of a micromuscle according to thepresent invention;

FIGS. 6A and 6B show a seventh embodiment of the present invention;

FIGS. 7 to 9 illustrate an example of application of the presentinvention to a end-to-side anastomosis operation;

FIGS. 10 to 12 illustrate an example of application of the presentinvention to a clipping operation; and

FIGS. 13A and 13B illustrate an example of application of the presentinvention to a vessel obturation operation.

The present invention provides a micromuscle or micro-engine that canoperate in a biological medium. This micromuscle comprises a chamberformed at least partially of a semipermeable membrane enabling transferof a solution by osmosis and containing a solute likely to dissolve in afluid contained in the biological medium. The solute will be selected tobe unable to cross said semipermeable membrane. Its presence induces anosmotic pressure likely to cause liquid transfers towards the chamber;the solute will thus be said to be “osmotically active”.

The chamber may be placed in compressed or folded form in a selectedarea of a biological medium, for example, at a given level of an artery,via a catheter or an endoscope. Once the micromuscle has been arranged,molecules from the solution in which it is placed tend to cross thesemipermeable membrane and the micromuscle takes a desired shape underthe effect of the penetration of a biological liquid, for example,water, into the chamber.

Examples of micromuscle shapes and structures are given in FIGS. 1 to 6.

FIG. 1A is a perspective view of a torus-shaped micro-muscle inexpansion. At rest, this micromuscle has either a flattened and possiblyfolded shape such as shown in FIG. 1B or a compressed or reduced shapeas shown in FIG. 1C.

FIG. 2A is a side view of a micromuscle of cylindrical shape inexpansion. At rest, this micromuscle has either a flattened or possiblyfolded shape such as shown in FIG. 2B or a cylindrical shape ofcompressed or reduced volume as shown in FIG. 2C.

The chamber such as illustrated for example in FIGS. 1A and 2A may beformed of a semipermeable membrane, possibly formed of a thinsemipermeable layer deposited on a porous or perforated supportmaterial. This membrane may be resilient or not. For example, to expandfrom the shape shown in FIG. 1B or 2B to the shape shown in FIG. 1A or2A, the chamber material needs not be resilient. However, in the case ofFIGS. 1C and 2C, the chamber material is a resilient material thatexpands as adapted.

Various means may be provided to control the final shape and/or thechamber expansion. For example, the chamber will be provided with fibersor surrounded with a net to control its final shape after expansion(flowing of the liquid of the biological medium towards the inside ofthe chamber).

As illustrated in FIG. 3A, the chamber may be formed, on a portion ofits surface, of a semipermeable non-expandable membrane, little or notdeformable, the rest of its surface being made of a deformable andpossibly resilient material connected to the semipermeable membrane. Achamber 1, for example, torus-shaped, made of a resilient material, maybe used, the internal volume of which communicates with the internalvolume of fibers 2 such as the fibers currently used in hemodialysisoperations. The liquid penetrating into fibers 2 will fill up chamber 1and expand it under the effect of the osmotic pressure. This compositeembodiment comprising a first portion formed of an elastic membrane, forexample, made of the product sold under trade name Silastic, and asecond portion formed of a semipermeable membrane, possibly in the formof fibers, preferably flexible, can adapt to most of the embodiments ofthe present invention as should be noted by those skilled in the art.

The micromuscle may also be formed of closed fibers with semipermeablewalls, initially in a folded state, which tend to straighten and stiffenunder the effect of the osmotic pressure.

In FIG. 3B, fibers 2 are arranged within a deformable torus-shapedchamber.

In FIG. 3C, fibers 2 are directly arranged within a cylindrical elementto which an expansion force is desired to be applied, for example, ablood vessel. In both cases, the fibers, initially containing moleculesenable of crossing the membrane at a concentration greater than theconcentration of the biological fluid in molecules themselves unable tocross the membrane, will tend to inflate and straighten, and thus tocentrifugally urge the surface surrounding it, once placed in abiological fluid. For the fibers to take, once stiffened, the helicoidalshape illustrated in FIG. 3C, they may be attached in places, possiblyslidably, before inflating, to a flexible sheath not shown or to thevessel walls.

In a first version, an assembly of parallel osmotic fibers is sewn tothe fabric that forms the wall. The path of any one of these fibers hasa spiral shape. When the pressure increases within the fiber, the latterwill tend to maximize its volume, and will thus tend to decrease itsradius of curvature. Both ends of the osmotic fiber are strongly securedto a specific point of the wall. However, the sewing of the osmoticfiber to the wall is sufficiently loose for the fiber to be able toslide with respect to the wall. The internal diameter of the helix maythus increase, and the wall will tend to expand. The shape taken by theassembly will result from the balance of the centripetal forces exertedby the osmotic fibers and from the resistance against the expansionexerted by the wall.

Various alterations of this version may be envisaged. For example,inextensible wires parallel to the generators of the cylinder formed bythe wall may be attached in various fashions (sewing, gluing . . . )thereto. The attachment is performed to create regular spacings betweenthe inextensible wires and the wall, through which the fibers may pass.These inextensible wires may possibly be semi-rigid rods.

In a second version, the osmotic fibers are directly integrated into thefabric, to the frame of which they take part. An assembly of fibers, forexample, made of Dacron, is arranged to form a series of parallel wires.The osmotic fibers are then crossed with this series of parallel wires.Various pattern shapes may be created by the crossing of Dacron fibersand osmotic fibers (for example, the osmotic fibers may have ahelicoidal shape, an arrowhead shape . . . ). In an alternative, thefabric is only formed of osmotic fibers.

It should be noted that such a device may find applications outside ofthe field of vascular endoprosthesis design. Indeed, a bag formed ofsuch a fabric can behave as a pump, the motions of which are conditionedby the relative concentration of the liquid medium inside of the bag andof the internal medium of the fibers in osmotically active substances.

FIGS. 4A and 4B show a fourth embodiment of the present invention,respectively in a state where the micromuscle is contracted, such as itis when put into place, and in a state where it is expanded, after itsputting into place and the setting of the osmotic pressure within thechamber. Two half-cylinders 4 and 5 slide one inside of the other. Eachof half-cylinders 4 and 5 is closed at its end opposite to the otherhalf-cylinder. Within internal half-cylinder 4 are arranged one orseveral chambers with a semipermeable wall 6 within which are moleculesunable to cross the membrane, not shown. The opposite ends of the twohalf-cylinders are connected by a wire 7 to limit their extension. As anexample, the system in the folded state may have a diameter on the orderof 100 μm and a length on the order of from 1 to 3 mm, this length beingsubstantially twice in the unfolded state. The device of FIGS. 4A and 4Bmay be called a microengine, an active element such as a needle beinglinkable to one of its ends.

FIG. 5A shows another embodiment of the present invention in whichseveral torus-shaped osmotic micromuscles 8 according to the presentinvention are connected to one another by a net or flexible wires 9, forexample, made of Dacron. The toruses may be distant from one another, asshown, or adjacent.

FIG. 5B shows another example of a composite micro-muscle, theelementary torus-shaped micromuscles being designated with referencenumeral 8 and the connection wires or nets with reference numeral 9.

It should be noted by those skilled in the art that the micromuscleaccording to the present invention is likely to have many otherembodiments, and especially many other shapes. It may for example be abag likely to expand and to take the shape of internal walls of a cavityin which it is placed, for example, to fill a cavity such as an aneurismof a brain vessel or other.

Various solutes, not harmful for the organism in case of a leak, may beused. A known solute is for example albumin, which is not let through bythe hemodialysis membrane.

FIGS. 6A and 6B illustrate a seventh embodiment of the presentinvention, usable in particular when the micromuscle according to thepresent invention must be inserted into a possibly humid, but non-liquidbiological medium. In this case, it may no longer be possible to “pump”the water from the organism. A device comprising two chambers orcompartments E1 and E2 communicating through an osmotic membrane M isthen provided. In an initial state, compartment E2 contains a fluid andcompartment E1 contains a solute likely to dissolve into the fluid ofcompartment E2. Thus, as illustrated in FIG. 6B, compartment E1 willtend to “inflate” by penetration through membrane M of the fluidcontained in compartment E2, the solute contained into compartment E1dissolving in this fluid. Each of these compartments has a deformable,tight, and biocompatible external envelope. In the example of embodimentillustrated in FIGS. 6A and 6B, chamber E2 has, firmly attached to it, alarge number of tight fibers similar to hair or tentacles incapable ofobturating a duct or of exerting a force on its walls. However,compartment E1 will have not effect on the walls of a duct in which itis arranged in the “deflated” state illustrated in FIG. 6A, but it willhave an obturating or pressure effect in the “inflated” state shown inFIG. 6B. Compartment E1 may have any desired shape, for example, theshape of an inflatable bag illustrated in the drawings or a torus,cylindrical or other shape.

For an insertion into the human body, for example, into a duct or vesselwhich is desired to be obturated or on the walls of which an action isdesired to be exerted, the micromuscles of FIGS. 6A and 6B will first beplaced into a catheter in compressed form, that is, compartment E1 willhave a reduced volume, the fluid that it contains being pushed out bythe pressure towards compartment E2. As soon as the device is put intoplace, compartment E1 is free to expand and the fluid contained incompartment E2 fills in this compartment which then exerts a desiredaction in the medium in which it is placed.

Various alterations of this embodiment may be provided. For example, aswill be described hereafter, compartment E1 may comprise moleculestrapped in a protective envelope or likely to chemically react withother molecules to be activated only when desired. Similarly,compartment E2 may contain non-free solute molecules likely to bereleased only as a consequence of a physical or chemical action. In thissecond case, it is possible to “deflate” compartment E1 after insertionand inflating.

Control of the Expansion of an Osmotic Micromuscle

According to an aspect of the present invention, a method forcontrolling the expansion of a micromuscle according to the presentinvention is provided. This control may be chemical or physical.

Chemical Control

According to an embodiment of this aspect of the present invention, themicromuscle may contain a solute A likely to react with a body B and toform therewith a solute C, the number of formed molecules of solute Cbeing larger than the number of molecules of solute A consumed uponreaction between A and B. Body B is capable of crossing thesemipermeable membrane and solutes A and C are incapable thereof. Body Bis then injected into the biological medium, for example, by means of aninjection needle. It should be understood that, by performing successiveinjections, successive “inflatings” of the micromuscle can be performed.Thus, if for example an artery is desired to be expanded, a lightexpansion may be performed, and subsequently increased. The intervalbetween two injections may be long and will be chosen according to theorganism's reactions to the micromuscle.

An implementation of this embodiment is based on the concept of“competition” between chemical bodies. The principle is that a body Acan combine, for example, in non-covalent fashion, with two bodies B andC. If A and C are put together in a solvent, a complex A-C will thusform. If, now, B is introduced into the solution, and if B has a greater“affinity” for A than C's for A, B will “move” C: the C molecules willbe released, and a complex A-B will form.

This competition principle may be used to increase the osmotic force,for example as follows. Derivatives of specific proteins, such as avidinor streptavidin, covalently bonded to “attachment matrixes” (any solidbody used as a support) are used. These proteins play the function ofbody A for which a competition will occur between body B and body C.Proteins A have the specificity of being able to bind in non-covalentfashion with a molecule of small molecular weight, HABA(4-hydroxyazobenzene-2-carboxylic acid). Body C will be obtained by“grafting” the HABA on a molecule having a sufficient molecular weightnot to cross the semipermeable membrane. At the time of its introductioninto the organism, the chamber thus contains an attachment matrix, towhich is bound in non-covalent fashion, via proteins A, body C. C beingattached to the matrix is thus not in solution and has no osmoticeffect. A “biotin” derivative, which plays the role of body B, is thenintroduced into the organism. Biotin is a vitamin with a low molecularweight, naturally present in the organism. Biotin has the specificity ofhaving a very strong affinity for avidin and for streptavidin, muchstronger than HABA's affinity for these proteins. Thus, molecules ofbody C detach from the attachment matrix and form a solute that tends toincrease the solution pressure within the chamber.

A, as well as B, will be chosen to obtain a selective affinity of B forA: these molecules will have a very strong reciprocal affinity, whilenatural biotin will have a lesser affinity for A. The low molecularweight of B will enable it to easily cross the semipermeable membrane.The affinity of B for A will make it compete with C to set on A, thusreleasing from the matrix the HABA, and thus, body C, which will then beable to exert its osmotic effect.

It should be noted that it is possible to attach to the matrix, insteadof a derivative of avidin or streptavidin, a derivative of HABA,provided to take as C the result of a fusion of a “large” molecule witha derivative of avidin or streptavidin. As in the preceding case, theinjection of a biotin analog will “release” C, by competition with HABA.

This alternative, in which C comprises an avidin or streptavidinderivative, has the advantage of enabling partial reversibility of thedesired osmotic effect. It is indeed known to generate moleculescomprising not a single site having an effect analogous to that ofbiotin, but two such sites. Call B′ such a molecule (which will becalled the “dimer” biotin analog form, as opposed to the previously-used“monomer” biotin analog form, which has a single attachment site for anavidin or streptavidin derivative). After C has been released from thematrix (by injection of a monomer biotin analog form), if a dimer biotinanalog form is injected, the dimer form will compete with the monomerform. If the dimer form concentration is sufficient, it will move themonomer form from the avidin or streptavidin derivative sites of C. Thiswill translate as the forming of C-B′-C complexes, thus reducing thenumber of molecules in solution, and thus the osmotic effect. Theprocess may be repeated, by injecting again in a sufficient quantity thebiotin analog monomer form. In this case, indeed, the competition willbecome favorable to the forming of C-B complexes, which increases backthe number of molecules in solution.

Although the method has been described to control the osmotic effect ofa micromuscle, it also applies to the controlled release of activeprinciples, thus providing an alternative to “implantable syringe” typedevices. Such devices exist, and are formed of “tanks” containing theproduct. Said product is ejected from the tanks under the effect of aphysical power source (gas under pressure, osmotic pressure, breakage ofthe tank wall under the effect of ultrasounds . . . ). Thepreviously-described competition principle has in its application tosuch devices the advantage of enabling accurate control of the time whenthe active principle is released (which is an advantage with respect togas or osmotic effect syringes), and of not requiring use of any devicecapable of generating and of directing the external power source (whichis an advantage with respect to methods using, for example,ultrasounds). It is enough, to achieve this specific object, for body Cwhich will be released to be the active principle of which the releaseis desired to be controlled, and to be able to cross the chamber inwhich it is. As soon as the adequate competitor B is introduced into theorganism (for example, sublingually, by ingestion or by injection), itwill release body C, thus enabling it to diffuse into the organism andto express its medical effect.

It should be noted that, in this alternative of the present invention,the use of a matrix is no longer indispensable, since it is no longeraimed at controlling the osmotic effect. In this case, call C the resultof the combination between the active principle and HABA, and call A theresult of the fusion between an avidin derivative and a “large”molecule. A and C, put together in the same solution, form an A-Ccomplex. The device inserted into the organism comprises a chamberlimited by a membrane impermeable to A-C, but permeable to C, as well asto biotin derivative B. The introduction of B into the organism willmove C, which can thus diffuse into the organism.

It should further be noted that the chamber used is not necessarilyartificial. There indeed exist in the organism regions into which onlycertain very specific molecule sorts can penetrate. The naturalfrontiers of these regions can thus play the function of thepreviously-used semipermeable membrane. The cephalo-rachidian liquid isan example of such a region, which has the advantage of being easilyaccessible (for example, by lumbar puncture). Such a region can thus beused as a “tank” and an active principle C such as that discussed in thepreceding paragraph can be introduced thereinto, for example, bypuncture. Couple (C, B) will in this case be chosen so that B is likelyto reach the region of interest. It should be noted that, in thespecific case of the cerebrospinal liquid, the release of C will beperformed mainly into the areas of cerebrospinal liquid resorption,which are located in the brain. This is particularly advantageous if thepreferential activity of C expresses in the brain (L-DOPA, for example,which is a precursor of dopamin, used in the treatment of Parkinson'sdisease).

It should also be noted that an alternative of the exploitation of thecompetition properties provided by biotin derivatives may beimplemented. Consider a protein having a large internal cavity likely tobe used as a tank (such is for example the case for certain “chaperon”proteins such as GroEL, or ferritin). It is possible to configure thisprotein so that HABA molecules are located at the level of its“aperture” and so that the attachment of avidin or streptavidin proteinsis likely to close the cavity. Such a mechanism enables “encapsulating”a large amount of active principle molecules. The introduction of biotininto the organism moves part of the avidin “plugs”, thus releasing partof the encapsulated molecules. This system requires for the“tank-protein” and “plug-protein” complexes to be in a medium ensuringtheir stability and a protection of the immune system, and for thismedium to be sensitive to variations of the biotin ratio in the blood.Such conditions can be imposed in an artificial chamber isolated fromthe organism by an adequate membrane, or obtained in a natural chamberlike the cerebrospinal liquid.

It should finally be noted that the provided examples are based on thespecific case of the competition between biotin derivatives and avidinor streptavidin derivatives, but that the same results can be obtainedwith other systems of competition between molecules.

Physical Control

According to an embodiment of this aspect of the present invention, thecontrol can be performed physically, for example by placing part atleast of the solute in one or several microcapsules so that it hasinitially no or little activity. The microcapsules can then be broken,possibly selectively, by means of an external power source, for example,ultrasounds, a magnetic field, or a laser. A body likely to dissolve themicrocapsules may also be injected.

It should be noted that physical power may be directly used to “break”molecules into smaller molecules, which has an effect upon the osmoticproperties of the solution thus performed. Macromolecules such as DNAmay be broken by the application of ultrasounds (this technique iscommonly used in molecular biology). The longer the ultrasounds areapplied, the more the average fragment size decreases. In an alternativeof the present invention, large-size DNA fragments (obtained for exampleby any protocol of purification of the bacterial DNA, or by “polymerasechain reaction” from the genetic material of the individual to betreated) are placed inside of a semipermeable membrane chosen not to letthrough such large-size fragments. After the application of ultrasounds,the number of fragments and, accordingly, the osmotic force, increase.The membrane may be chosen to let through DNA fragments of sufficientlysmall size. In this case, a sufficiently prolonged application ofultrasounds enables releasing part of the DNA from within the membrane,and thus decreasing the osmotic force. It should however be noted thatin this alternative, the osmotic force cannot be increased backafterwards.

APPLICATION EXAMPLES

Various examples of applications of an osmotically-inflatablemicromuscle according to the present invention will now be described.

1. Vascular Endoprostheses

Methods are known for treating an aneurism, that is, a loss of theparallelism of the edges of a vessel, which translates as an expansionof a vascular segment, consisting of inserting into the vessel, at theexpansion level, a cylinder, for example made of a shape-memorymaterial, which is arranged to obturate the communication between thevessel and the aneurism. However, the vessel appears in practice toexpand along time and the blood flowing through the vessel can againcommunicate with the aneurism.

To solve this problem, the present invention provides using, instead ofthe shape-memory cylinder, a cylinder formed from an osmotic micromuscleaccording to the present invention. According to an alternative of thepresent invention, it is provided to use a conventional vascularendoprosthesis formed of a shape-memory material, and to arrange at bothends of this prosthesis a torus-shaped osmotic micromuscle which willbehave as a seal of variable and controllable diameter. Indeed, asindicated previously, it may be provided to progressively inflate thistorus-shaped micromuscle, at regular intervals, to take into accountdeformations of the vessel.

2. Progressive Vascular Expansion

Known vessel expansion vascular methods are based on the use of “stents”or ring-shaped springs which are inserted inside of a blood vessel at alocation where said vessel is stenosed. Such stents conventionally usememory-shape alloys and face the problem of “restenosis”, that is, afterhaving being increased by the expansion gesture, the vessel diametersecondarily decreases, thus depriving the patient of the benefit of thepresent invention.

The applicant considers that this restenosis is for the most part due tothe aggressive character of the expansion. Indeed, with conventionalmethods, this expansion is performed very rapidly, in certain caseswithin a few seconds for shape-memory stents and within a few minutesfor mechanically-inflated stents. The vessel diameter can be increasedby a factor on the order of 2 or more. This results in an inflammatoryreaction which will exert on the stent a constrictive effort sufficientto deform it.

The use of a torus-shaped micromuscle according to the present inventionenables solving this problem, given that it can be adjusted to veryprogressively “inflate”, for example, within several days. On the otherhand, as indicated previously, successive methods for activating themicromuscle according to the present invention may be provided and, atregular intervals, for example, one week, one month or more, themicromuscle may be “reinflated” to perform a very progressive expansionof the vessel to be expanded.

A micromuscle according to the present invention may appear under aparticularly small volume in the non-contracted state and can thuseasily be inserted by conventional means such as catheters or endoscopesat any desired location.

3. Vessel Suture

3.1. End-to-Side Anastomosis

Coronary artery bypass usually uses a derivation of an artery (forexample, the internal mammary artery), which is mobilized andanastomosed just downstream of the stenosed area (end-to-sideanastomosis). The diameters of the thinnest coronaries on which suchgestures are performed are on the order of from 1.5 mm to 2 mm. Thepresent invention provides a device enabling sewing while respecting thepressure in the vessel (here, the coronary), to ease its handling.

3.1.1. Preparation of the Mammary

The mammary artery may be “equipped” with various mechanisms intended toease its anastomosis with the coronary. It is indeed possible tointroduce a catheter into the free end of the mammary, and to inflate asmall balloon around this catheter, which will enable attaching to thisend the mechanisms adapted to those which will subsequently equip thecoronary (at the possible cost of the subsequent sacrifice of the fewvessel millimeters located downstream of the end balloon).

3.1.2. Forming of a “Buttonhole” on the Coronary

A catheter having dimensions smaller than one millimeter is introducedinto the coronary, at the level desired for the anastomosis. Thisintroduction can be performed through the femoral.

The catheter comprises a guide. This guide may be immobilized at twopoints located upstream and downstream of the area to be anastomosed (bymeans of two clips seizing the coronary).

On guide 10 is assembled a “foldable harrow”. This harrow is illustratedin unfolded position in FIG. 7A. It is formed of two ranks of needles11. The needle shapes and dimensions are those currently used to enablesewing of the coronaries. Typically, their base diameter is on the orderof a few hundreds of micrometers, and their length is on the order of afew millimeters. At their base, the needles are firmly attached to asingle wire 12. This wire defines two sub-assemblies of “right-hand” and“left-hand” needles. The wire first connects the “right-hand” needleassembly, the bases of which are aligned (or form a very elongatedhalf-ellipse), then the “left-hand” needle assembly (see FIG. 9).

The needles are arranged so that the harrow can take two limitingconfigurations. In the “catheter” configuration, illustrated in FIG. 7B,the needles are elongated along the catheter axis. In the “sewing”configuration, illustrated in FIG. 7A, the needles are perpendicular tothis axis. According to the present invention, the raising of the harrowuses at least one “osmotic motor” comprising a first small balloon 13arranged on the lower side of the harrow and one or several second smallballoons 14 arranged on the upper side of the harrow and arranged tosurround the needles. One or the other of osmotic motors 13 and 14 maybe replaced with its hydraulic or pneumatic equivalent.

Once the harrow is in place, to enable perforation of the coronary,balloon 13 located under the harrow is “inflated” while “balloons” 14intended to erect the needles keep their initial pressure. This thenleads to the position illustrated in FIG. 8.

When an “osmotic” mechanism is used, these operations are implemented invery natural fashion. The small balloons are indeed deflated when thecatheter is introduced. The latter may be protected by a cap, whichavoids for these balloons to be in contact with a hydrous medium. Theremoval of this cap puts the balloons in contact with the blood medium,which activates the osmotic mechanism. If, for example, theosmotically-active bodies have been introduced with a concentrationtwice smaller in balloons 14 intended to erect the needles than inballoon 13 intended to place these needles flat against the oppositewall, the needles will first erect, then be placed back against thewall, and finally perforate said wall.

3.1.3. Mammary and Coronary Anastomosis

The harrow needles must be used, once they have perforated the coronarywall.

The mammary may have been equipped with a mechanism enabling holding theneedles (for example, triple collar, each needle passing before thefirst collar, behind the second one, and before the third one). Thecollars are then stretched, which firmly attaches the collars to theneedles.

The mammary may have been equipped with a mechanism equivalent to thecoronary's. The “coronary” needles must then be immovably attached tothe “mammary” needles. Various simple mechanisms can be envisaged(welding, gluing, “twisting” of one needle around the other, etc.).

It may also be devised for the “right-hand” needles to be all raised, toform a series of wire “bridges”, under which a cable having its two endsattached to the mammary is introduced. The motions to be performed arehere very simple. When the “right-hand” needles have been firmlyattached to the mammary, the same operation is performed for the“left-hand” needles.

3.1.4. Opening of the Communication Between Mammary and Coronary

Up to this stage, the circulation in the coronary has not beeninterrupted, and the arterial circulation of the mammary is not yetconnected to the coronary's. However, the sewing is now ended. Thecoronary wall still has to be perforated, on its component locatedbetween the two rows of needles. The flow pressure will “round up” thisopening.

The perforation may be performed mechanically, from an intra-mammarycatheter. It may also be electrically devised. The intra-coronarycatheter guide is indeed placed flat against the area to be perforated.If it conducts the current, and if it is bare over this area (the restbeing isolated), a current can flow through the intra-mammary catheterand the intra-coronary catheter, the assembly behaving as an electriclancet.

The balloons are finally deflated, and the coronary and mammarycatheters can then be removed.

3.2. Osmotic Clipping

In vascular surgery, clipping is an advantageous alternative to sewing,since it enables “confronting” two vessels without leaving material incontact with the vascular bed. A mechanical stapler has been describedby T. Richard in “AAA: Laparoscopic and/or endovascular repair?”,Angio-Techniques 2001. The vessel end is arranged on an “anvil”, whichenables turning over the free edge, and then having a sufficiently rigidsupport to enable bearing of the clips.

The disadvantages of this system are:

-   -   a relative complexity of the stapler,    -   the need to use an intermediary vascular substitute (indeed, the        stapler must be able to “enter” through the free end of a        vessel; the two terminal ends to be anastomosed are thus        “equipped”, after which an adequate device enables restoring the        continuity),    -   the difficulty of miniaturizing the system.

To overcome these disadvantages, the present invention provides anosmotic clipping device.

First, the free end of each vessel is prepared as follows. An elastic“bag”, exhibiting on a portion at least of its surface a semipermeablemembrane, is introduced into the vessel. This bag, when inflated, hasthe shape illustrated in FIGS. 10A and 10B respectively in side view andin top view:

-   -   it has a rotational symmetry,    -   one of its ends 20 is cylindrical,    -   medium 21 is conical,    -   the other end comprises digitations 22.

As illustrated in FIGS. 11A to 11C, the bag is introduced while“deflated” into a vessel 24 (FIG. 11A). A ring 25 with as manyprotrusions 26 as there are intervals between the digitization isinstalled on vessel 24 (FIG. 11B). Finally, the bag is “inflated”.

The different steps of the assembling of two sections of a vessel areillustrated in FIGS. 12A to 12C. The two sections, equipped as thatshown in FIG. 11C, are shown opposite to each other as illustrated inFIG. 12A.

Care has been taken over the positioning of protuberances 26 of rings 25in the spaces left empty by digitizations 22. The protrusions supportedby one of the rings are the “male” portions of “press studs”, thosesupported by the other ring being the “female” portions of the same“press studs”.

The protuberances are positioned opposite to one another, incomplementary fashion, and the rings are then brought close to eachother (FIG. 12B) before fastening the “press buttons” (FIG. 12C). Beforeblocking the last press button element(s), the bags are deflated (forexample, by being perforated by means of a needle). In their deflatedform, they may be extracted through the orifice remaining between thetwo vessels.

In the present section 3.2, only the case where the “bags” intended toexpand the vessel orifices and to prepare the assembly of the ringsprovided with protrusions are of osmotic micromuscle type. It should benoted that pneumatically-inflating balloons or shape-memory devices mayalso be used to perform this operation.

4. Reversible Obturation of a Vessel

A micromuscle according to the present invention may also be used insideof a duct or vessel as a valve that may be opened or closed.

An embodiment of such a valve is illustrated in FIG. 13A in openposition and in FIG. 13B in closed position inside of a duct or vessel41. An endoprosthesis or stent of cylindrical shape 42 formed forexample of a shape-memory alloy is surrounded on its median portion witha sleeve 43 formed of a ring-shaped osmotic micromuscle arranged betweenthe cylinder and the vessel. In the case where the vessel walls areresilient, the stent diameter is selected to be slightly greater thanthat of the vessel to enable anchoring of the stent in the vessel. Theexpansion capacity of the micromuscle, upon contact with the vesselwall, makes it exert a radial force that compresses both the stent andthe wall. The respective forces exerted by the stent and by themicromuscle will be selected to result in the complete obturation of thevessel. One of the previously-described means may be used to stop thecompression effect exerted by the micromuscle and “reopen” the vessel.

Such a valve may for example be used for the reversible obturation ofthe Fallopian tubes. Indeed, the ligature of the Fallopian tubes(natural duct with a diameter of a few millimeters linking the ovariesto the uterus) is used as a contraceptive means. However, this techniqueresults in a quasi-definitive sterilization, possible surgicalinterventions intended to restore the functionality of these tubeshaving a high failure ratio.

If a valve of the above-mentioned type is inserted into each of the twotubes, the device operates as a contraceptive means. The introduction ofthe stent into the tube may be carried out through the vagina orpossibly by laparoscopy. When the woman wants to stop this effect, thetube functionality is simply restored.

It can be feared that the internal medium of the Fallopian tubes, thoughhumid, is insufficiently liquid to have a direct action upon an osmoticmicromuscle likely to attract a liquid from the surrounding medium. Inthis case, it will be chosen to use a micromuscle according to theseventh embodiment of the present invention, illustrated in relationwith FIGS. 6A and 6B, which has its own liquid reserve. In thisapplication, a reversible micromuscle will preferably be used, that is,a micromuscle in which the second compartment is likely under the effectof a physical or chemical action to “deflate” the first compartment. Thecontraceptive action is then made reversible.

It should be noted by those skilled in the art that it is also possibleto directly use the capacity of acting as a “plug” of the seventhembodiment of the present invention. In this case, the micromuscle isinserted into the Fallopian tube, that it obturates. If later thepatient wants to have children again, one of the previously-describedmicromuscle control modes is applied and enables deflating compartmentE1. Nothing then “blocks” the micromuscle any longer in the Fallopiantube, and it naturally falls in the uterine cavity, from which it willbe evacuated at the next menstrual period. This specific embodiment hasthe disadvantage of requiring a new setting into place of the device, ifthe contraceptive function is subsequently wanted back. It however hasthe advantage of not leaving a foreign body in the organism, which maypose psychological and physiological problems (the mobility of the tubewall is indeed a significant element of the female fertility, and thepermanent presence of a stent could negatively affect it).

Among the many alterations and modifications of the present inventionwhich will occur to those skilled in the art, it should be noted thatmost of the applications of osmotic micromuscles which have beendescribed may be implemented by using devices having, in theseapplications, functions similar to those of the osmotic micromuscles,for example, pneumatic or shape-memory devices.

1. A micromuscle device for immersion in a biological medium, themicromuscle device comprising a deformable chamber having at least aportion formed of a semipermeable membrane, the deformable chambercontaining a solute capable of being osmotically active, the deformablechamber being designed to have, after inflating by osmotic effect, apredetermined shape, wherein the deformable chamber is surrounded with asheath or net that determines the predetermined shape, wherein thesolute is activable by a product injectable into the biological medium,and wherein the solute is bound to an attachment matrix by a firstchemical body from which it can detach in consequence of a competitionwith another chemical body.
 2. The micromuscle device of claim 1,wherein the solute is bound to avidin molecules, the avidin moleculesbeing bound to the attachment matrix by HABA molecules, this bond beingbreakable by competition with vitamin derivatives, including biotinderivatives, having a greater affinity for the avidin molecules than forthe HABA molecules.
 3. The micromuscle device of claim 2, wherein thevitamin derivatives include monomer and dimer forms of biotinderivatives.
 4. A micromuscle device for immersion in a biologicalmedium, the micromuscle device comprising a deformable chamber having atleast a portion formed of a semipermeable membrane, the deformablechamber containing a solute capable of being osmotically active, thedeformable chamber being designed to have, after inflating by osmoticeffect, a predetermined shape; wherein the solute is activable by aproduct injectable into the biological medium; and wherein the solute isbound to HABA molecules, the HABA molecules being bound to an attachmentmatrix by proteins, including at least one of avidin or streptavidinderivatives, this bond being breakable by competition with vitaminderivatives, including biotin derivatives, having a greater affinity forthe proteins than for the HABA molecules.
 5. A micromuscle device forimmersion in a biological medium, the micromuscle device comprising adeformable chamber having at least a portion formed of a semipermeablemembrane, the deformable chamber containing a solute capable of beingosmotically active, the deformable chamber being designed to have, afterinflating by osmotic effect, a predetermined shape, wherein thedeformable chamber is formed of two half-cylinders sliding one inside ofthe other.
 6. The micromuscle device of claim 5, wherein opposing endsof the two half-cylinders are connected by a wire.
 7. A micromuscledevice for immersion in a biological medium, the micromuscle devicecomprising a deformable chamber having at least a portion formed of asemipermeable membrane, the deformable chamber containing a solutecapable of being osmotically active, the deformable chamber beingdesigned to have, after inflating by osmotic effect, a predeterminedshape, wherein the semipermeable membrane of the micromuscle deviceseparates the deformable chamber from a second chamber that is incommunication with the semipermeable membrane, and wherein the secondchamber is formed of a flexible material and contains a reserve of aliquid capable of forming a solution with the solute contained in thedeformable chamber.
 8. The micromuscle device of claim 7, wherein thesolute is capable of being released by physical or chemical action.